Fidanacogene elaparvovec

The use of fidanacogene elaparvovec in patients receiving hepatotoxic medication or using hepatotoxic substances is limited. Use of hepatotoxic medications or substances may reduce the efficacy of fidanacogene elaparvovec, and the risk of serious hepatic reactions may increase following administration.

Prior to fidanacogene elaparvovec infusion, ensure patients are up to date on their vaccinations. If concomitant corticosteroid administration is needed following fidanacogene elaparvovec infusion, delay administration of live vaccines until the patient has been weaned off corticosteroids.

Monitor patients with risk factors for hepatocellular carcinoma (e.g., hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic steatohepatitis, advanced age) with regular liver ultrasound (e.g., annually) and alpha-fetoprotein testing for 5 years following fidanacogene elaparvovec.

Fidanacogene elaparvovec is not intended for administration in women. There are no data from the use of fidanacogene elaparvovec in pregnant women. No animal reproductive studies have been conducted with fidanacogene elaparvovec.

In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

There is no information regarding the presence of fidanacogene elaparvovec in human milk, the effect on the breastfed infant, and the effects on milk production.

Fidanacogene elaparvovec is not intended for administration in women.

Carcinogenicity, mutagenicity, reproductive toxicity, and impairment of fertility studies have not been conducted with fidanacogene elaparvovec. In a 2-year vector integration study in NHPs administered 5 × 10¹² vg/kg, vector DNA was mostly detected in the form of episomal DNA that was not integrated into the host genome. The integration sites were generally random with a low frequency, and there was no indication of significant clonal expansion.

The most common adverse reaction (incidence ≥5%) reported in clinical studies was an increase in transaminases.

Clinical trials experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of fidanacogene elaparvovec was evaluated in 60 [45 patients in clinical study 1 (NCT03861273) and 15 patients in clinical study 2 (NCT02484092)] patients who received the recommended dose (5 × 10¹¹ vg/kg) in two open-label clinical studies.

No serious adverse reactions were reported in patients treated with fidanacogene elaparvovec. The most common adverse reactions observed in ≥5% of patients post-dose are listed in the following table:

Adverse reactions (incidence ≥5%) following treatment with fidanacogene elaparvovec:

^* Includes terms alanine transaminase (ALT) increased, aspartate transaminase (AST) increased, hepatic enzyme increased, hepatic function abnormal, liver function test abnormal, transaminases increased.

Not all transaminase elevations were reported as adverse reactions.